[unreadable] [unreadable] After extensive review by several scientific and regulatory authorities worldwide, aspartame was found to be safe and approved for use in carbonated beverages in 1983, followed by approval for general purpose in 1996. Since then, aspartame found its way into more than 6,000 products in the US and today is one of the most commonly used artificial food sweeteners worldwide. However, concerns about a potential health threat posed by aspartame, particularly with regard to its carcinogenic effects, have remained and resurfaced after a 2006 study, which reported a dose dependent increase in lymphomas, leukemias and renal tumors in 1,800 rats tested at aspartame doses much lower than the currently acceptable daily intake for humans. Subsequent results from the NIH-AARP Diet and Health Study did not support these animal data. However, given the study's one-time measure and short follow-up, concerns about the validity of these results remain. We propose to use the unique resources of two large, NIH-funded cohort studies, the Nurses' Health Study and the Health Professionals Follow-up Study, with prospectively and repeatedly collected information on diet to assess the risk of cancer in relation to aspartame intake. In these two cohorts combined, there are 1,501 lymphoma and leukemia cases, 726 bladder cancer cases, and 20,730 overall incident cancer cases with up to 20 years of follow-up (1984-2004). Using Cox proportional hazards models to adjust for age and other potential confounding factors, we will evaluate associations between estimated total aspartame intake as well as major dietary sources of aspartame intake such as diet soda and breakfast cereal (as identified by brand name) and the risk of leukemia, lymphoma, bladder cancer, and overall cancer risk, using repeated measurements. In this application, we will directly address concerns about the potential carcinogenic effect of aspartame in humans. We will be able to examine consistent and long-term exposure to aspartame from food in a unique way. Using extensively validated dietary assessments updated over time to reflect current food levels, this study will be the most detailed and thorough analysis on the effects of aspartame on cancer risk in humans to date. Because we have been assessing intake since aspartame was first allowed into the food supply, we are effectively capturing lifetime aspartame exposure. Our results may help decision-makers formulate guidelines and direct future aspartame studies. Even a null finding would be important in this context. [unreadable] [unreadable] [unreadable]